ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3851G>A (p.Arg1284Gln) (rs149462407)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001081471 SCV000289344 likely benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455463 SCV000540092 uncertain significance not specified 2016-10-31 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has not been reported in affected individuals. It is present in ExAC at a MaxMAF of 0.1%. It is classified in ClinVar as Likely Benign (1 star - Invitae). 11 mammals have a Gln at this position.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000455463 SCV000602036 likely benign not specified 2017-03-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000566885 SCV000671267 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
GeneDx RCV000455463 SCV000729737 likely benign not specified 2017-09-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics,PreventionGenetics RCV000679625 SCV000806767 uncertain significance not provided 2017-03-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000455463 SCV000920079 likely benign not specified 2018-12-14 criteria provided, single submitter clinical testing Variant summary: POLE c.3851G>A (p.Arg1284Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00062 in 267992 control chromosomes. The observed variant frequency is approximately 43 fold of the estimated maximal expected allele frequency for a pathogenic variant in POLE causing Colorectal Cancer phenotype (1.4e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.3851G>A in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (3 likely benign and 3 VUS). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679625 SCV001148891 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing

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